Ver­sant care­ful­ly sets the stage for a $68M de­but of a biotech play­er fo­cused on syn­thet­ic lethal­i­ty

Over the past 18 months, the grow­ing team at Re­pare Ther­a­peu­tics has been qui­et­ly set­ting up shop in Ver­sant Ven­tures’ dis­cov­ery ops and fo­cus­ing on syn­thet­ic lethal­i­ty — the ther­a­peu­tic in­ter­play be­tween ge­net­ic mu­ta­tions and can­cer. Us­ing CRISPR gene edit­ing tech as an in­ter­ro­ga­tion tool, they’ve been play­ing with well known tar­gets like p53 and BR­CA1 to find out how they con­spire with oth­er mu­ta­tions in the de­struc­tion of a ma­lig­nan­cy, fol­low­ing the trail of le­sions in the pur­suit of new ther­a­pies that can work in the same fun­da­men­tal way those PARP in­hibitors you’ve been hear­ing so much about can fight can­cer.

The goal was to mas­ter syn­thet­ic lethal­i­ty and iden­ti­fy the first cou­ple of tar­gets to go af­ter in the clin­ic. They lined up their team, now at 20, li­censed in dis­cov­ery work from NYU on a poly­merase im­pli­cat­ed in nu­mer­ous can­cers, and to­day will come out of stealth mode with a $68 mil­lion round and at least a four-year run­way with plans to start tack­ling clin­i­cal work in late 2019.

Their first pro­gram in­volves DNA-di­rect­ed DNA poly­merase theta — PolQ — in­clud­ed in a path­way that re­pairs dou­ble-strand breaks in can­cer cells. And while they have a ways to go be­fore they be­gin hu­man stud­ies, the in­vestors are send­ing a mes­sage that the amount of cash they’re bet­ting on Re­pare in­di­cates a high lev­el of con­fi­dence for their longterm suc­cess.

Jer­el Davis

“In terms of the in­cu­ba­tion pe­ri­od,” says Jer­el Davis, man­ag­ing di­rec­tor at Ver­sant, “this com­pa­ny is de­cep­tive­ly ma­ture.”

“The time we’ve been able to spend in stealth al­lowed us to build the com­pa­ny out of the spot­light,” says CEO Lloyd Se­gal. In Mon­tre­al they have de­vel­oped their med­i­c­i­nal chem­istry team un­der Cameron Black, the for­mer head of chem­istry at Mer­ck Frosst who joined a lit­tle more than a year ago. And when Ver­tex re­cent­ly shut down in Mon­tre­al, they swooped in, grab­bing an ex­pe­ri­enced team with a long track record of work­ing to­geth­er.

Lloyd Se­gal

With­in hours of the shut­down, they had 13 new re­cruits out of 14 of­fers.

R&D head Michael Zin­da, who led As­traZeneca On­col­o­gy iMed Bio­science group in Boston, is head­ing up the oth­er group in Cam­bridge, MA.

Ver­sant has gath­ered an im­pres­sive group of mar­quee in­vestors to back their up­start. MPM Cap­i­tal came in along­side as the lead in­vestor on the Se­ries A, with Cel­gene’s Swiss of­fice tak­ing part along with FTQ and BDC Ven­tures.

“We could have tak­en more mon­ey,” Se­gal tells me. “We had more than that on the ta­ble. But we be­lieved that was the kind of mon­ey that we hope will take two com­pounds in­to the clin­ic in late ’19 or ear­ly 2020.”

Ver­sant had a front row seat on some of the ear­ly work on syn­thet­ic lethal­i­ty at Clo­vis while it was work­ing on PARP, says Davis. “This is a field we know and our con­vic­tion is that PARP is the tip off the ice­berg.”

Re­pare has the plat­form that they plan to use to map out some of the rest of the un­ex­plored ter­ri­to­ry.

Even with­out R&D part­ners Se­gal feels that he has enough cash to make their way through at least the first 4 years. Add in the prospect of some ma­jor league play­ers com­ing in to part­ner on key prospects, and that run­way will stretch fur­ther. If it all plays out ac­cord­ing to plan, Se­gal adds, this will be their last ven­ture raise.

It’s an am­bi­tious plan, with some stel­lar sci­en­tif­ic ad­vis­ers ready to leaned guid­ance. The full sci­en­tif­ic ad­vi­so­ry board in­cludes:

– Samuel Apari­cio, pro­fes­sor in the de­part­ment of pathol­o­gy and lab­o­ra­to­ry med­i­cine at the Uni­ver­si­ty of British Co­lum­bia.

– Jim Carmichael, head of the pro­tein home­osta­sis the­mat­ic cen­ter of ex­cel­lence at Cel­gene. He pre­vi­ous­ly was UK re­gion­al di­rec­tor of med­ical sci­ence at As­traZeneca fol­low­ing its ac­qui­si­tion of Ku­DOS, where he was CMO and re­spon­si­ble for clin­i­cal de­vel­op­ment of ola­parib.

– Ron­ny Drap­kin, di­rec­tor of the Penn Ovar­i­an Can­cer Re­search Cen­ter and di­rec­tor of gy­ne­co­log­ic can­cer re­search at the Uni­ver­si­ty of Penn­syl­va­nia.

– Lau­rie Glim­ch­er, pres­i­dent and CEO of the Dana-Far­ber Can­cer In­sti­tute.

– Mark Pe­gram, di­rec­tor of the breast can­cer on­col­o­gy pro­gram at Stan­ford Women’s Can­cer Cen­ter and co-di­rec­tor of Stan­ford’s mol­e­c­u­lar ther­a­peu­tics pro­gram.

– Richard Wood, pro­fes­sor of mol­e­c­u­lar bi­ol­o­gy at the Uni­ver­si­ty of Texas MD An­der­son Can­cer Cen­ter.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Wen Wang, IASO CEO

Chi­nese CAR-T play­er books a megaround to dri­ve bustling cell ther­a­py port­fo­lio through the clin­ic

China has quickly emerged as a major driver of oncology R&D in recent years, particularly in cell therapies where the potential for cheaper development has investors drooling. Now, one player, with a handful of early data, is swimming in a new round of investor cash.

IASO Bio has closed a $108 million Series C that the Chinese and California-based biotech said it will use to advance its slate of cell therapy lead programs, while also propping up a roster of next-gen allogeneic cell therapies for the future, according to a release.

Multiple antibiotic resistant Pseudomonas aeruginosa bacterium

A new way to in­fil­trate (and de­stroy) some of the dead­liest drug-re­sis­tant bugs

About four years ago, Ruben Tommasi, the gregarious scientific chief of antibiotics startup Entasis, walked into a meeting with his top chemist and top biologist to chew over another batch of unchanging results.

“It felt like we were running the same experiment over and over,” Tommasi told Endpoints News. “We had all sort of come to that point in time where we felt like we were banging our heads against the wall.”

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